The landmark study that first brought worldwide attention to the potential of St. John's wort was a meta-analysis of 23 controlled studies, published in 1996 in the British Medical Journal by Klaus Linde of Ludwig-Maximilians University in Munich Germany and Gil Ramirez and Cindy Mulrow, now at the San Antonio Evidence-Based Practice Center at the University of Texas. The meta-analysts concluded that there is evidence that St. John's wort is "more effective than placebo for the treatment of mild to moderately severe depressive disorders."

The American College of Physicians-American Society of Internal Medicine(ACP-ASIM) in May, 2000, released new guidelines for the treatment of depression with drugs, including the advice that "St. John's wort may be effective in treating mild depression in the short term," though they had some caveats about its use.

For the full text of the organization's clinical guidelines, including its advice about St. John's wort, published in the May 2, 2000, Annals of Internal Medicine

The ACP-ASIM clinical guidelines are based on a systematic review of newer pharmacotherapies for depression in adults, including the literature on St. John's wort, published in the May 2, 2000, Annals of Internal Medicine.

That systematic review was, in turn, based on a 1999 report, "Treatment of Depression: Newer Pharmacotherapies," prepared by Cynthia Mulrow and her colleagues at the San Antonio Evidence-based Practice Center at the University of Texas Health Science Center for the Agency for Heath Care Policy and Research (now Agency for Healthcare Research Quality).

The beneficial effects of St. John's wort seen in more than a dozen European studies led the National Institutes of Health to make it the subject of the first federally-funded, large-scale trial of an herbal supplement. NIH has enrolled 336 volunteers, who will be given either a placebo, a standardized extract of St. John's wort (LI-160), or a prescription antidepressant (Zoloft) for eight weeks. The investigators have completed their recruitment of volunteers.

The first large-scale U.S. trial of St. John's wort was completed this spring. Sponsored by Pfizer (which makes the antidepressant Zoloft), the study's results were presented at the annual meeting of the American Psychiatric Association on May 17, 2000, by the lead investigator, Richard C. Shelton of Vanderbilt University. The study abstract is not published online. Here are the details available thus far:

200 outpatients with major depression (SCID-DSM-IV), who were healthy, free of psychotropic drugs at the beginning of the study, and who had a baseline 17-item-Ham-D score of greater than 19 were recruited at 11 U.S. university medical centers. They were randomly assigned either a placebo or 900mg a day of a standardized St. John's wort extract (LI-160) for eight weeks. If there was not an adequate response to 900 mg a day of St. John's wort after four weeks, the dose was then advanced to 1200 mg a day. Assessments included the HAM-D,Ham-A, BDI, and CGI. "The data suggest that SJW is no more effective than placebo in patients with major depression of at least moderate severity." The rate of side effects from SJW appeared to be no different from the placebo.

Why might the first U.S. trial of St. John's wort contradict the previous research?

"Some of the earlier studies in Europe were conducted in primary-care practice settings with physicians who may not have had any experience with research in depression," Shelton told CSPI. "We selected highly respected researchers herein the U.S. who were more experienced with doing a study on depression."

The head of the U.S. branch of Lichter Pharma, the German company that developed the LI-160 extract of St. John's wort, told CSPI that company scientists believe the Vanderbilt study was poorly designed and executed, but he could not explain why. Lichter Pharma has no response on their U.S. or German Web sites.

Does St. John's wort elevate mood?

All the relevant studies on St. John's wort have been conducted on people suffering from clinical depression. However, U.S. dietary supplement manufacturers cannot claim on their labels that St. John's wort is useful in the treatment of depression because the the Food and Drug Administration (FDA) has not approved the herb for use against this disease. Instead, manufacturers advertise that St. John's wort elevates mood or fights the blues, which are legal claims since "low mood" or "the blues" are not considered diseases, but there is no scientific evidence to substantiate any benefit from St. John's wort.

The National Institutes of Health is currently recruiting participants to test whether St. John's wort can alter mood in normal, healthy volunteers.

As late as 1998, the German Commission E Monograph for St. John's wort stated that there were no known interactions between St. John's wort and other drugs. That is no longer true. In early 2000, two shocking reports of serious interactions between the herb and important medications were published in The Lancet.

The first by Steven Piscitelli and his colleagues at the National Institutes of Health revealed that St. John's wort depresses blood levels of indinavir, a protease inhibitor used to treat AIDS, to the point where the levels are probably no longer effective. (AIDS patients sometimes take St. John's wort for depression.)

For Health Canada's letter to Canadian physicians, pharmacists, and practitioners of complementary medicine, including a table of identified or suspected interactions between prescription drugs and St. John's wort

The most recent analysis of commercial St. John's wort products was conducted in March, 2000, by www.vitacost.com, a commercial site that sells dietary supplements. They tested eight popular brands and found only two--Nature's Way Standardized Extract and Natrol's Mood Support--contained an appropriate dosage of hyperforin, now widely regarded as probably the most important active ingredient in St. John's wort. Vitacost.com defined an appropriate dosage of hyperforin as 27mg a day.

On January 10, 2000, the Boston Globe published an analysis of seven popular brands of St. John's wort products. Only one product--Nature's Resource--contained at least 0.3% hypericin. Only two products--Quanterra and Nature Made--passed a biological assay developed by Paracelsian, Inc., of Ithaca, New York, which tests the ability to block the reuptake of both serotonin and dopamine, two neurotransmitters involved in depression.

For the full text of the Boston Globe article on how they did their testing

On August 31, 1998, the Los Angeles Times published the results of a laboratory analysis of ten standardized St. John's wort products. Only three--Nature's Herbs, Nature's Resource, and Safeway Select, contained at least 90% of the hypericin levels listed on the package labels. Three others contained no more than about half the listed amount--Futurebiotics, Pure Source, and Sundown Herbals. (The Rexall Sundown company disputed the results, though a second lab commissioned by the Times confirmed that the brand contained only about 20% of the claimed amount of hypericin.)

In March, 1998, the Good Housekeeping Institute reported finding a 17-fold variation in the levels of hypericin in six popular brands of St. John's wort capsules and a seven- to eight- fold difference in three popular liquid extracts, according to a laboratory analysis commissioned by the Institute. The National Nutritional Foods Association (NNFA), a trade association of health food store and dietary supplement manufacturers, vigorously disputed the findings, claiming that the Institute failed to take variations in capsule weight, non active ingredients, and dosage into account. Good Housekeeping has no information on their Web sites about their analysis and did not respond to repeated requests for a response to the NNFA criticisms. NNFA, likewise, does not have information about the dispute on their Web site.